CORNELL UNIV./A. RAYNER
Theory and practice: taking notes from Harold Varmus (left); loading acrylamide gels (right).
This summer, a small group of chemistry graduates at Cornell University went off to study biology at research laboratories in Manhattan. The students are the fourth group to enter an innovative multi-institution programme to produce scientists skilled in chemical biology, a cross-disciplinary field that promises to create a new breed of biomedical researcher.
The philosophy of the scheme, the Tri-Institutional Training Program in Chemical Biology, is to attract chemistry students into biomedical science. Although that was a popular move in the 1950s and 1960s, says programme director Timothy Ryan, it became less appealing as biochemistry morphed into molecular biology. In the post-genomic era, with researchers taking a quantitative approach to areas such as protein and cell biology, biologists are finding that they again need support from the physical sciences.
"Biomedical science really needs people with that training," Ryan notes. "Chemistry has some very nice niches and some very useful tools, which can be applied to some interesting areas of biology."
The challenge for training institutions is that few graduates with a physics and chemistry background want to commit themselves to a biology programme. They think they won't fit into the different culture, or would lose the benefits of their previous training. The idea behind the tri-institutional programme is to let them remain in a chemistry atmosphere while giving them as many biological problems to solve as possible.
The programme is a collaboration by Cornell's chemistry department at Ithaca and three institutions based in New York city: Cornell's Weill Medical College, Rockefeller University and the Memorial Sloan-Kettering Cancer Center. Students alternate laboratory rotations and seminars in the city with advanced chemistry courses at Ithaca, plus an intensive course in biomedical science, before joining the laboratory of their chosen research adviser at any of the four centres. The rotation gives them a mix of basic chemistry, basic biomedical research and clinical research — all important components in the drug-discovery and drug-development pipeline.
Ten-Year View
"We try to make new ties between the chemistry department at Ithaca and the biomedicine community down here," says Ryan, a biochemistry professor at Weill. "One of the connectors is the students, and we try to teach them as much biology as we can. Even if we don't capture them now, when they move on to their next position they'll be more attuned to working on biologically relevant problems. The success will be measured in maybe ten years' time when we see if we've placed into the research community a new breed of people with this hybrid training."
Harold Varmus, president of the Memorial Sloan-Kettering Cancer Center, says that there is a definite trend towards such cross-disciplinary projects. "All science is becoming much more interactive, especially at the intersection of chemistry and biology. We're focusing on that when building graduate programmes, so that people actually get trained in both disciplines, as opposed to learning one as a student and trying to obtain the other later on," he says.
The Cornell programme is one of a new generation of interdisciplinary graduate courses in chemical biology — the use of chemical tools and principles to solve problems in biology. Demand is driven by the need to make the most of information coming from genomic and proteomic research. The courses aim to deepen understanding of protein structure and chemistry and of the role such structures play in cell functions.
In the United States, the National Institutes of Health has made chemical biology central to its 'roadmap' for medical research. One of the document's main themes is that progress in medicine will require quantitative knowledge about the interconnected networks of molecules that comprise cells and tissues, along with improved insights into how these networks are regulated and how they interact.
Chemical skills and approaches will be invaluable in identifying and synthesizing small molecules to use as probes in studying the properties and interactions of proteins and ligands, as well as in designing and synthesizing new therapeutic compounds.
Chemical Tools for Biological Problems
"The principal tools are those of synthesis, analysis, structure–function determination and mechanistic investigation," says Lawrence Marnett, director of the Vanderbilt Institute of Chemical Biology (VICB) in Nashville, Tennessee. Learning to use these chemical tools on biological problems will offer invaluable perspectives on a range of areas including drug discovery, structural biology and signal transduction.
The VICB, established in 2002 by Vanderbilt University's College of Arts and Science and School of Medicine, supports students from the different departments through three separate graduate programmes. "These provide students with an exceptional diversity of opportunities for pedagogical and laboratory training," notes Marnett. "An increasing number of students come from strong basic-science undergraduate programmes and want to apply their skills to important biomedical research problems."
Many universities now offer graduate programmes in chemical biology (see Web links). Although most take only chemical graduates — believing it is too hard for a biologist to make the leap to chemistry — others will take talented students from the life sciences.
The emergence of chemical biology is also reinvigorating chemistry. This is important in places such as the United Kingdom, where university courses in such traditional fields are often undersubscribed.
"We need to make these disciplines more attractive by going into areas such as chemical biology and nanotechnology," says Hagan Bayley, who last year became the first professor of chemical biology at the University of Oxford. "Many of these things exist already, but often you're just putting new labels on them so that people can recognize them, and to make these areas more attractive to students and to funding."
VANDERBILT UNIV.
Lawrence Marnett sees an exceptional diversity of opportunities.
Bayley heads what he calls a "sub-department" within the chemistry department. Chemical-biology teams occupy a whole floor of the university's new £60-million (US$110-million) Chemistry Research Laboratory, and he is encouraging interactions across projects and disciplines.
"People are tending to do research more at the interface of different traditional disciplines, and that has created a need for undergraduate and graduate programmes in those areas," says Bayley. Such programmes will be developed over the next few years.
In Britain, chemical biology has been identified as a priority area by the Biotechnology and Biological Sciences Research Council, with the emphasis on protein chemistry and exploiting genomic data. The Engineering and Physical Sciences Research Council and the Medical Research Council are jointly soliciting research proposals for new applications of chemical tools to biomedical research. Several universities, including Newcastle upon Tyne and Warwick, already offer undergraduate degrees in chemical biology.
Ireland boasts the Centre for Synthesis and Chemical Biology (CSCB), a government-backed collaboration between University College Dublin, Trinity College Dublin and the Royal College of Surgeons in Ireland. New laboratories are being built for the centre, attached to University College's chemistry department. The CSCB has a student-exchange programme with the Centre for Medicinal Chemistry at the University of Regensburg, Germany, and is establishing links in Asia.
"We take the big view of 'molecules to medicine'," says director Pat Guiry. "It's not just synthesis for the sake of synthesis — there's a lot of collaboration with biologists where chemists can make suggestions about how to change the molecule to change its effect in vivo."
With 40 principal investigators and about 55 postdocs, the centre has some 120 PhD students, most with a chemistry background. "In some cases people who've done a chemistry degree are moving to biochemistry, but there's not as much movement as one would wish to see," says Guiry. "There's a culture change in how things are done, and people are starting to look outside the box. This is one of the centres helping to promote that sort of attitude."
The true test of this training will be when the current students emerge into the mainstream of research and apply their skills to some of biomedicine's most pressing questions.
Web links
Cornell Tri-Institutional Training Program in Chemical Biology
http://www.med.cornell.edu/tpcb
Vanderbilt Institute of Chemical Biology
http://www.vanderbilt.edu/vicb
Harvard Molecular, Cellular and Chemical Biology training programme
University of California, Berkeley, Chemical Biology graduate programme
http://cbgp.cchem.berkeley.edu
University of California, San Francisco, Chemistry and Chemical Biology graduate programme
University of Michigan Chemical Biology Interface training programme
Skaggs Institute for Chemical Biology
University of Oxford Department of Chemistry
University College Dublin Centre for Synthesis and Chemical Biology
